Hormonal
High-fat diet feeding induces an early and sustained infiltration of pro-inflammatory macrophages (CD11c+CD11b+F4/80+) into skeletal muscle, which correlates with insulin resistance and is dependent on the chemokine CCL2.
In the context of obesity and high-fat diets, skeletal muscle undergoes a specific immune response where pro-inflammatory macrophages infiltrate the tissue, driven by the chemokine CCL2. This infiltration is directly linked to the development of insulin resistance. While this is a mechanistic finding primarily from mouse models, it suggests that chronic high-fat intake triggers a local immune response in muscle that impairs glucose disposal, independent of simple caloric excess.
CD11c+ proinflammatory macrophages in muscle increased by 76%. After 10 weeks HFD, macrophages in muscle increased by 47%. Quadriceps from CCL2-KO mice on HFD did not gain macrophages and maintained insulin sensitivity.
Why this rating
Strong mechanistic evidence in mice (WT vs KO, multiple time points) supported by human observational data (biopsies correlating with clamp data).
Source
Pro‐Inflammatory macrophages increase in skeletal muscle of high fat‐Fed mice and correlate with metabolic risk markers in humans
Lisbeth N. Fink et al. · Obesity · 2013
DOI 10.1002/oby.20615
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